202 research outputs found
Detection of GD2-positive cells in bone marrow samples and survival of patients with localised neuroblastoma
The impact of bone marrow (BM) GD2-positive cells on survival has been evaluated in 145 Italian children with localised neuroblastoma (NB) evaluated at diagnosis by anti-GD2 immunocytochemistry. Nineteen of these (13.1%) were found to be BM GD2-positive, with the number of positive cells ranging between 1 and 155 out of 1 × 106 total cells analysed. Seven/19 (38.8%) GD2-positive vs 12/126 (9.5%) GD2-negative patients relapsed. The 5-year event-free survival (EFS) and overall survival of the GD2-positive patients was significantly worse than that of the GD2-negative ones (62.2 vs 89.9%, P<0.001; and 74.9 vs 95.9%, P=0.005, respectively). GD2 positivity was not associated to other known risk factors, and in particular to Myc-N amplification and 1p deletion. Among Myc-N-negative patients, the EFS of those negative for both GD2 and 1p deletion was significantly better than in children positive for either one of these two markers (EFS=96.9 vs 66.0%, P<0.001). In conclusion, GD2 positivity may represent a prognostic marker for patients with non-metastatic NB without Myc-N amplification, and its combination with genetic alterations might help identifying patients that require a more careful follow-up
LSST Science Book, Version 2.0
A survey that can cover the sky in optical bands over wide fields to faint
magnitudes with a fast cadence will enable many of the exciting science
opportunities of the next decade. The Large Synoptic Survey Telescope (LSST)
will have an effective aperture of 6.7 meters and an imaging camera with field
of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over
20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with
fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a
total point-source depth of r~27.5. The LSST Science Book describes the basic
parameters of the LSST hardware, software, and observing plans. The book
discusses educational and outreach opportunities, then goes on to describe a
broad range of science that LSST will revolutionize: mapping the inner and
outer Solar System, stellar populations in the Milky Way and nearby galaxies,
the structure of the Milky Way disk and halo and other objects in the Local
Volume, transient and variable objects both at low and high redshift, and the
properties of normal and active galaxies at low and high redshift. It then
turns to far-field cosmological topics, exploring properties of supernovae to
z~1, strong and weak lensing, the large-scale distribution of galaxies and
baryon oscillations, and how these different probes may be combined to
constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at
http://www.lsst.org/lsst/sciboo
Cucurbitacin I Inhibits Cell Motility by Indirectly Interfering with Actin Dynamics
Cucurbitacins are plant natural products that inhibit activation of the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway by an unknown mechanism. They are also known to cause changes in the organization of the actin cytoskeleton. actin depolymerization experiments, cucurbitacin I had no effect on the rate of actin filament disassembly at the nanomolar concentrations that inhibit cell migration. At elevated concentrations, the depolymerization rate was also unaffected, although there was a delay in the initiation of depolymerization. Therefore, cucurbitacin I targets some factor involved in cellular actin dynamics other than actin itself. Two candidate proteins that play roles in actin depolymerization are the actin-severing proteins cofilin and gelsolin. Cucurbitacin I possesses electrophilic reactivity that may lead to chemical modification of its target protein, as suggested by structure-activity relationship data. However, mass spectrometry revealed no evidence for modification of purified cofilin or gelsolin by cucurbitacin I.Cucurbitacin I results in accumulation of actin filaments in cells by a unique indirect mechanism. Furthermore, the proximal target of cucurbitacin I relevant to cell migration is unlikely to be the same one involved in activation of the JAK2/STAT3 pathway
A cis-regulatory module activating transcription in the suspensor contains five cis-regulatory elements
Spatiotemporal DNA methylome dynamics of the developing mouse fetus
Cytosine DNA methylation is essential for mammalian development but understanding of its spatiotemporal distribution in the developing embryo remains limited. Here, as part of the mouse Encyclopedia of DNA Elements (ENCODE) project, we profiled 168 methylomes from 12 mouse tissues or organs at 9 developmental stages from embryogenesis to adulthood. We identified 1,808,810 genomic regions that showed variations in CG methylation by comparing the methylomes of different tissues or organs from different developmental stages. These DNA elements predominantly lose CG methylation during fetal development, whereas the trend is reversed after birth. During late stages of fetal development, non-CG methylation accumulated within the bodies of key developmental transcription factor genes, coinciding with their transcriptional repression. Integration of genome-wide DNA methylation, histone modification and chromatin accessibility data enabled us to predict 461,141 putative developmental tissue-specific enhancers, the human orthologues of which were enriched for disease-associated genetic variants. These spatiotemporal epigenome maps provide a resource for studies of gene regulation during tissue or organ progression, and a starting point for investigating regulatory elements that are involved in human developmental disorders
Low exposure long-baseline neutrino oscillation sensitivity of the DUNE experiment
The Deep Underground Neutrino Experiment (DUNE) will produce world-leading
neutrino oscillation measurements over the lifetime of the experiment. In this
work, we explore DUNE's sensitivity to observe charge-parity violation (CPV) in
the neutrino sector, and to resolve the mass ordering, for exposures of up to
100 kiloton-megawatt-years (kt-MW-yr). The analysis includes detailed
uncertainties on the flux prediction, the neutrino interaction model, and
detector effects. We demonstrate that DUNE will be able to unambiguously
resolve the neutrino mass ordering at a 3 (5) level, with a 66
(100) kt-MW-yr far detector exposure, and has the ability to make strong
statements at significantly shorter exposures depending on the true value of
other oscillation parameters. We also show that DUNE has the potential to make
a robust measurement of CPV at a 3 level with a 100 kt-MW-yr exposure
for the maximally CP-violating values \delta_{\rm CP}} = \pm\pi/2.
Additionally, the dependence of DUNE's sensitivity on the exposure taken in
neutrino-enhanced and antineutrino-enhanced running is discussed. An equal
fraction of exposure taken in each beam mode is found to be close to optimal
when considered over the entire space of interest
Identification and reconstruction of low-energy electrons in the ProtoDUNE-SP detector
Measurements of electrons from interactions are crucial for the Deep
Underground Neutrino Experiment (DUNE) neutrino oscillation program, as well as
searches for physics beyond the standard model, supernova neutrino detection,
and solar neutrino measurements. This article describes the selection and
reconstruction of low-energy (Michel) electrons in the ProtoDUNE-SP detector.
ProtoDUNE-SP is one of the prototypes for the DUNE far detector, built and
operated at CERN as a charged particle test beam experiment. A sample of
low-energy electrons produced by the decay of cosmic muons is selected with a
purity of 95%. This sample is used to calibrate the low-energy electron energy
scale with two techniques. An electron energy calibration based on a cosmic ray
muon sample uses calibration constants derived from measured and simulated
cosmic ray muon events. Another calibration technique makes use of the
theoretically well-understood Michel electron energy spectrum to convert
reconstructed charge to electron energy. In addition, the effects of detector
response to low-energy electron energy scale and its resolution including
readout electronics threshold effects are quantified. Finally, the relation
between the theoretical and reconstructed low-energy electron energy spectrum
is derived and the energy resolution is characterized. The low-energy electron
selection presented here accounts for about 75% of the total electron deposited
energy. After the addition of lost energy using a Monte Carlo simulation, the
energy resolution improves from about 40% to 25% at 50~MeV. These results are
used to validate the expected capabilities of the DUNE far detector to
reconstruct low-energy electrons.Comment: 19 pages, 10 figure
Long-baseline neutrino oscillation physics potential of the DUNE experiment
The sensitivity of the Deep Underground Neutrino Experiment (DUNE) to neutrino oscillation is determined, based on a full simulation, reconstruction, and event selection of the far detector and a full simulation and parameterized analysis of the near detector. Detailed uncertainties due to the flux prediction, neutrino interaction model, and detector effects are included. DUNE will resolve the neutrino mass ordering to a precision of 5σ, for all ΑCP values, after 2 years of running with the nominal detector design and beam configuration. It has the potential to observe charge-parity violation in the neutrino sector to a precision of 3σ (5σ) after an exposure of 5 (10) years, for 50% of all ΑCP values. It will also make precise measurements of other parameters governing long-baseline neutrino oscillation, and after an exposure of 15 years will achieve a similar sensitivity to sin22θ13 to current reactor experiments
Long-baseline neutrino oscillation physics potential of the DUNE experiment
The sensitivity of the Deep Underground Neutrino Experiment (DUNE) to neutrino oscillation is determined, based on a full simulation, reconstruction, and event selection of the far detector and a full simulation and parameterized analysis of the near detector. Detailed uncertainties due to the flux prediction, neutrino interaction model, and detector effects are included. DUNE will resolve the neutrino mass ordering to a precision of 5σ, for all δ_(CP) values, after 2 years of running with the nominal detector design and beam configuration. It has the potential to observe charge-parity violation in the neutrino sector to a precision of 3σ (5σ) after an exposure of 5 (10) years, for 50% of all δ_(CP) values. It will also make precise measurements of other parameters governing long-baseline neutrino oscillation, and after an exposure of 15 years will achieve a similar sensitivity to sin²θ₁₃ to current reactor experiments
First results on ProtoDUNE-SP liquid argon time projection chamber performance from a beam test at the CERN Neutrino Platform
The ProtoDUNE-SP detector is a single-phase liquid argon time projection chamber with an active volume of 7.2× 6.1× 7.0 m3. It is installed at the CERN Neutrino Platform in a specially-constructed beam that delivers charged pions, kaons, protons, muons and electrons with momenta in the range 0.3 GeV/c to 7 GeV/c. Beam line instrumentation provides accurate momentum measurements and particle identification. The ProtoDUNE-SP detector is a prototype for the first far detector module of the Deep Underground Neutrino Experiment, and it incorporates full-size components as designed for that module. This paper describes the beam line, the time projection chamber, the photon detectors, the cosmic-ray tagger, the signal processing and particle reconstruction. It presents the first results on ProtoDUNE-SP\u27s performance, including noise and gain measurements, dE/dx calibration for muons, protons, pions and electrons, drift electron lifetime measurements, and photon detector noise, signal sensitivity and time resolution measurements. The measured values meet or exceed the specifications for the DUNE far detector, in several cases by large margins. ProtoDUNE-SP\u27s successful operation starting in 2018 and its production of large samples of high-quality data demonstrate the effectiveness of the single-phase far detector design
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